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Development of a cell adhesion-based prognostic model for multiple myeloma:Insights into chemotherapy response and potential reversal of adhesion effects

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Oncology Research 2024年第4期32卷 753-768页

作者： QIAN HU MENGYAO WANG JINJIN WANG YALI TAO TING NIU Department of Hematology West China HospitalSichuan UniversityChengdu610041China

Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical role.This study integrated four RNA sequencing datasets(CoMMpass,GSE136337,GSE9782,and GSE2658)and focused on analyzing 1706 adhesionrelated genes.Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes,including KIF14,TROAP,FLNA,MSN,LGALS1,PECAM1,and ALCAM,which demonstrated the strongest associations with poor overall survival(OS)in MM patients.To comprehensively evaluate the impact of cell adhesion on MM prognosis,an adhesion-related risk score(ARRS)model was constructed using Lasso Cox regression analysis.The ARRS model emerged as an independent prognostic factor for predicting OS.Furthermore,our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs,protein kinase inhibitors,and drugs targeting the PI3K/Akt/mTOR signaling pathway.Nevertheless,we identified promising drug candidates,such as tirofiban,pirenzepine,erlotinib,and bosutinib,which exhibit potential in reversing this resistance.In vitro,experiments employing NCIH929,RPMI8226,and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs.By employing siRNA-mediated knockdown of the key ARRS model gene KIF14,we observed suppressed proliferation of NCIH929 cells,along with decreased adhesion to BMSCs and fibronectin.This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM.Additionally,potential molecular mechanisms underlying adhesion-related resistance are proposed,along with viable strategies to overcome such resistance.These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.

关键词： cell adhesion Bioinformatics Prognosis Multiple myeloma CAM-DR

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Engineering Photocleavable Protein-decorated Hydrogels to Regulate cell adhesion and Migration

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Chemical Research in Chinese Universities 2022年第6期38卷 1512-1517页

作者： LI Tianyi HUANG Yaying LU Chenjing GU Liwen CAO Yi YIN Sheng Collaborative Innovation Center of Advanced Microstructures National Laboratory of Solid State MicrostructureDepartment of PhysicsNanjing UniversityNanjing210093P.R.China Jurong Country Garden School Zhenjiang

cell adhesion and migration play essential roles in tissue development and maintenance, and abnormal cell migration is involved in life-threatening diseases, including vascular disease, tumor formation, and metastasis. The advances in hydrogel-based 3D cell culture development facilitated the investigation of cell motility behavior, including cell-cell and cell-matrix adhesion and cell migration in a microenvironment more related to in vivo situations. Establishing advanced methods for these in vitro studies is thus necessary. Photo-sensitive proteins show advantages in remote and non-invasive regulation of hydrogels’ properties, and thus are of great potential in regulating 3D cultured cells’ behavior. In the presented study, we engineered photocleavable protein(PhoCl)-decorated hydrogels to regulate cell adhesion and migration of MDA-MB-231. The integrin-binding motif RGD was fused to the PhoCl and was decorated on the hydrogel. After being exposed to light at 405 nm, the PhoCl was cleaved and the RGD motif was released, resulting in detachment of the binding cells. The regulatory effect of the light illumination showed a time-dependent and cell density-dependent manner. Furthermore, the elimination of RGD by patterned light exposure completely suspended the cell migration to the corresponding region, suggesting a controllable regulation of the cell migration direction.

关键词： cell adhesion cell migration Photoresponsive protein Hydrogel Photoresponsive hydrogel Photocleavable protein

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Fluorine Substitution Tunes the Nanofiber Chirality of Supramolecular Hydrogels to Promote cell adhesion and Proliferation

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Advanced Fiber Materials 2023年第1期5卷 377-387页

作者： Huijie Lu Yu Zhao Shuchun Qin Yanyan Zhang Jinying Liu Jian Zhang Chuanliang Feng Weili Zhao Key Laboratory for Special Functional Materials of Ministry of Education School of Materials Science and EngineeringHenan UniversityKaifeng 475004China School of Pharmacy Institutes of Integrative MedicineFudan UniversityShanghai 201203China State Key Lab of Metal Matrix Composites School of Materials Science and EngineeringShanghai Jiao Tong UniversityShanghai 200240China

Fluorine atoms confer desirable biophysical,chemical,and biological properties to peptides/proteins by participating in various intermolecular interactions with their environment,but they are rarely used to control supramolecular chirality and functional.Herein,to identify the effects of fluorine substitution on the chirality and function of supramolecular assem-blies,C2-symmetric benzene-paradicarboxamide-based phenylalanine(phe)derivatives and three monofluorinated variants that had a single fluorine atom on their benzyl side chain in either the ortho,meta,or para position were synthesized.The experimental and theoretical results clearly show that the resulting assembled fibrils were supported by multiple interactions,including hydrogen bonding,π–πstacking and C/O–H…F–CAr interactions.Compared to nonfluorinated analogs,fluorine and its ring position on the aromatic side chain dictated the type and strength of the F···H interaction and then induced changes in supramolecular chirality and fiber morphology.Further studies on cell behavior showed that the order of positive interac-tion between high-order supramolecular chirality(M,P)and molecular chirality(L,D)on cell proliferation and viability is LM>DM>LP>DP.These findings provide a protocol for leveraging fluorine atoms and their positional dependence on directing chiral nanostructures with desirable handedness and creating fluorinated supramolecular hydrogels as extracellular matrix-mimetic scaffolds for cell culture and regenerative medicine.

关键词： Supramolecular chirality Helical inversion Fluorine substitution Positional effect cell adhesion

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Understanding the interplay between cell force and cell adhesion processes

再生工程(英文)

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再生工程(英文) 2023年第3期4卷 277-288页

作者： Peng Wang Jie Li Qiang Wei College of Polymer Science and Engineering State Key Laboratory of Polymer Materials and EngineeringSichuan UniversityChengdu610065China College of Biomass Science and Engineering Sichuan UniversityChengdu610065 China Department of cellular Biophysics Max Planck Institute for Medical ResearchUniversity of HeidelbergJahnstraße 2969120 HeidelbergGermany

cells,wrapped among their neighbors and surrounding extracellular matrix(ECM),form cell-cell adhesions and cell-ECM adhesions.Extracellular biophysical cues exert a far-reaching influence on a sweeping of cell behaviors,including signal transduction,gene expression,and fate determination.cell-cell adhesions mediated by inter-cellular adhesion molecules bridge the membranes of adjacent cells through either heterophilic or homophilic adhesive interactions,playing a critical part in multicellular structural maintenance and,therefore,a foundation for multicellular organisms.cell-ECM adhesions are derived from the interaction between cell adhesion receptors and multi-adhesive matrix proteins to ensure cell and tissue cohesion.Whereas cells not only unilaterally respond to certain cues from extracellular environment but can also alter the physicochemical profiles of the externalities and hence hold important implications for clinical applications.The essential function of cell adhesions has cre-ated tremendous interests in developing methods for measuring and studying cell adhesion properties,namely,cellular force.Here,we describe the collection of cell adhesive inputs on cellular signaling cascades and the“crosstalk”between cell-cell adhesions and cell-ECM adhesions.Furthermore,we provide the summary of the current methods to measure such cell adhesive forces.

关键词： cell adhesion cellular force Microenvironment Mechanotransduction cell force measurement

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cellular responses to nanoscale substrate topography of TiO_(2) nanotube arrays: cell morphology and adhesion

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Biomaterials Translational 2022年第3期3卷 221-233页

作者： Monchupa Kingsak Panita Maturavongsadit Hong Jiang Qian Wang Department of Chemistry and Biochemistry University of South CarolinaColumbiaSCUSA Computer Science Physicsand Engineering DepartmentBenedict CollegeColumbiaSCUSA

Nanotopographical features can be beneficial in augmenting cell functions and increasing osteogenic potential.However,the relationships between surface topographies and biological responses are difficult to establish due to the difficulty in controlling the surface topographical features at a low-nanometre scale.Herein,we report the fabrication of well-defined controllable titanium dioxide(TiO_(2))nanotube arrays with a wide range of pore sizes,30-175 nm in diameter,and use of the electrochemical anodization method to assess the effect of surface nanotopographies on cell morphology and adhesion.The results show that TiO_(2) nanotube arrays with pore sizes of 30 and 80 nm allowed for cell spreading of bone marrow-derived mesenchymal stem cells with increased cell area coverage.Additionally,cell adhesion was significantly enhanced by controlled nanotopographies of TiO_(2) nanotube arrays with 80 nm pore size.Our results demonstrate that surface modification at the nano-scale level with size tunability under controlled chemical/physical properties and culture conditions can greatly impact cell responses.These findings point to a new direction of material design for bone-tissue engineering in orthopaedic applications.

关键词： cell adhesion cellular responses morphology nanotopography TiO_(2)nanotube arrays

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cell adhesion AND SURFACE PROPERTIES OF POLYSTYRENE SURFACES GRAFTED WITH POLY(N-ISOPROPYLACRYLAMIDE)

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Chinese Journal of Polymer Science 2013年第11期31卷 1509-1518页

作者： Esmaeil Biazar Mohammad Taghi Khorasani Morteza Daliri Joupari Department of Biomedical Engineering Science and Research BranchIslamic Azad University Biomaterial Department of Iran Polymer and Petrochemical Institute National Research Center for Genetic Engineering and Biotechnology

cell adhesion plays a key role in various aspects of biological and medical sciences. In this study, poly（N- isopropylacrylamide）（PNIPAM） was grafted on polystyrene surfaces using different solvents under UV radiation. Moreover, the relation between surface roughness and cell adhesion were evaluated by gravimetric, SEM, AFM, contact angle measurement and cellular analyses. The gravimetric analysis clearly indicated an increase in the grafting by adding 10% methanol to water. The study of surface topography by AFM images showed an increase in the surface roughness and as a result of which, a decrease in wettablity was observed. At 37 ~C, epithelial ceils were well attached and proliferated on the grafted surfaces, while these cells were spontaneously detached below 32 ℃ in the absence of any enzymes. Moreover, MTT assay and SEM images indicated good cell viability and an increase in cell adhesion caused by the roughness increase. The results of this study reveal the great potential of PNIPAM-grafted polystyrene for being used in the biomedical fields such as drug delivery systems, tissue engineering and cell separation.

关键词： Grafting Solvent effect PNIPAM cell adhesion Surface roughness.

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An optimized method of culturing neurons based on polyacrylamide gel

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Biophysics Reports 2024年第1期10卷 41-47页

作者： Yongjing Qiao Jihong Gong Ziqi Jin Yiting Tu Xiaofei Yang Key Laboratory of Cognitive Science Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis & Treatment Laboratory of Membrane Ion Channels and Medicine College of Biomedical Engineering SouthCentral Minzu University

Substrate stiffness is a microenvironment with a certain stiffness constructed by the extracellular matrix and adjacent cells, which plays an important role in the growth and development of cells and tissue formation. Studies have indicated that the stiffness of the brain is about 0.1–1 kPa. The physiological and pathological processes of the nervous system are mediated by the substrate stiffness that the neurons suffer. However, how substrate stiffness regulates these processes remains to be studied. Culturing neurons on substrates with different stiffness in vitro is one of the best methods to study the role of stiffness in regulating neuronal development and activity. In this study, by changing the preparation time and the activation time of polyacrylamide gel, we provide an improved method that achieves a low toxic substrate environment for better primary neuron adhesion and development. Hope that this method is convenient for those studying the role of substrate stiffness in neurons.

关键词： Polyacrylamide gel Neuron culture cell adhesion Neural cell development

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cell Wall Microstructure Analysis Implicates Hemicellulose Polysaccharides in cell adhesion in Tomato Fruit Pericarp Parenchyma

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Molecular Plant 2009年第5期2卷 910-921页

作者： Jose J. Ordaz-Ortiz Susan E. Marcus J. Paul Knox Centre for Plant Sciences Faculty of Biological Sciences University of Leeds Leeds LS2 9JT United Kingdom

Methods developed to isolate intact cells from both unripe and ripe tomato fruit pericarp parenchyma have allowed the cell biological analysis of polysaccharide epitopes at the surface of separated cells. The LM7 pectic homogalacturonan epitope is a marker of the junctions of adhesion planes and intercellular spaces in parenchyma systems. The LM7 epitope persistently marked the former edge of adhesion planes at the surface of cells separated from unripe and ripened tomato fruit and also from fruits with the Cnr mutation. The LM 11 xylan epitope was associated, in sections, with cell walls lining intercellular space but the epitope was not detected at the surface of isolated cells, being lost during cell isolation. The LM15 xyloglucan epitope was present at the surface of cells isolated from unripe fruit in a pattern reflecting the former edge of cell adhesion planes/intercellular space but with gaps and apparent breaks. An equivalent pattern of LM15 epitope occurrence was revealed at the surface of cells isolated by pectate lyase action but was not present in cells isolated from ripe fruit or from Cnr fruit. In contrast to wild-type cells, the LM5 galactan and LM21 mannan epitopes occurred predominantly in positions reflecting intercellular space in Cnr, suggesting a concerted alteration in cell wall microstructure in response to this mutation. Galactanase and mannanase, along with pectic homogalacturonan-degrading enzymes, were capable of releasing cells from unripe fruit parenchyma. These observations indicate that hemicellulose polymers are present in architectural contexts reflecting cell adhesion and that several cell wall polysaccharide classes are likely to contribute to cell adhesion/cell separation in tomato fruit pericarp parenchyma.

关键词： cell walls fruit development tomato cell adhesion cell separation polysaccharide.

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Effect of chondroitin sulfate proteoglycans on neuronal cell adhesion, spreading and neurite growth in culture

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Neural Regeneration Research 2018年第2期13卷 289-297页

作者： Jingyu Jin Sharada Tilve Zhonghai Huang Libing Zhou Herbert M.Geller Panpan Yu Guangdong-Hongkong-Macao Institute of CNS Regeneration Ministry of Education Joint International Research Laboratory of CNS Regeneration Jinan University Laboratory of Developmental Neurobiology Cell Biology and Physiology Center National Heart Lung and Blood Institute National Institutes of Health

As one major component of extracellular matrix （ECM） in the central nervous system, chondroitin sul- fate proteoglycans （CSPGs） have long been known as inhibitors enriched in the glial scar that prevent axon regeneration after injury. Although many studies have shown that CSPGs inhibited neurite out- growth in vitro using different types of neurons, the mechanism by which CSPGs inhibit axonal growth remains poorly understood. Using cerebellar granule neuron （CGN） culture, in this study, we evaluated the effects of different concentrations of both immobilized and soluble CSPGs on neuronal growth, in- cluding cell adhesion, spreading and neurite growth. Neurite length decreased while CSPGs concentration arised, meanwhile, a decrease in cell density accompanied by an increase in cell aggregates formation was observed. Soluble CSPGs also showed an inhibition on neurite outgrowth, but it required a higher concen- tration to induce cell aggregates formation than coated CSPGs. We also found that growth cone size was significantly reduced on CSPGs and neuronal cell spreading was restrained by CSPGs, attributing to an inhibition on lamellipodial extension. The effect of CSPGs on neuron adhesion was further evidenced by interference reflection microscopy （IRM） which directly demonstrated that both CGNs and cerebral cortical neurons were more loosely adherent to a CSPG substrate. These data demonstrate that CSPGs have an effect on cell adhesion and spreading in addition to neurite outgrowth.

关键词： chondroitin sulfate proteoglycans cell adhesion neurite growth interference reflection microscopy neural regeneration

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Upregulation of cell adhesion through delta Np63 silencing in human 5637 bladder cancer cells

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Asian Journal of Andrology 2012年第5期14卷 788-792页

作者： Yun-Feng He Dai-Yin Tian Zheng-Jin Yi Zhi-Kang Yin Chun-Li Luo Wei Tang Xiao-Hou Wu Department of Urology The First Affiliated HospitalChongqing Medical UniversityChongqing 400016China Department of Respiratory Medicine Children's HospitalChongqing Medical UniversityChongqing 400014China Department of Urology Staffs'General Hospital of Panzhihua Iron and Steel Ltd Co.Panzhihua 617023China Faculty of Laboratory Medicine Chongqing Medical UniversityChongqing 400016China

Some researchs have demonstrated that the loss of delta Np63 is associated with aggressive phenotypes and poor prognosis. However, other research indicates that delta Np63 is considered to have oncogenic properties. Delta Np63 overexpression is often observed in association with the oncogenic growth of squamous cell carcinomas and bladder cancer. In this study, we investigated the oncogenic role of delta Np63 in regulating cell adhesion in transitional cell carcinoma of the bladder （TCCB）. The cells were stably transfected with the delta Np63 short hairpin RNA （shRNA） plasmid. Immunocytochemistry was performed to determine the knockdown efficiency. Tumour cells were studied for their ability to adhere to vascular endothelial cells. Confocal microscopy was used to analyse the changes in cytoskeletal F-actin. F-actin expression was measured by flow cytometry. cell invasion ability was assessed using transwell chambers. The delta Np63-silenced tumour cells were shown to adhere more tightly than controls to vascular endothelial cells （P〈0.05）. The content of F-actin in the delta Np63-silenced cells was enhanced （P〈0.05）. The Matrigel invasion assays showed that human 5637 bladder cancer cells had a lower degree of motility when transfected with pdelta Np63-shRNA （P〈0.05）. In conclusion, silencing of the delta Np63 expression can enhance the adhesiveness of 5637 cells by inducing F-actin cytoskeleton production, and it will possibly inhibit the TCCB invasion and metastasis.

关键词： bladder transitional cell carcinoma cell adhesion delta Np63

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